Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
The present disclosure relates to macrocyclic picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
One embodiment of the present disclosure may include compounds of Formula I:

wherein X is hydrogen or C(O)R3;
Y is hydrogen, C(O)R3, or Q;
Q is

R1 is hydrogen, alkyl, alkenyl, aryl, alkoxy, or acyl, each optionally substituted with 0, 1 or multiple R6;
R2 is hydrogen, alkyl, aryl, —Si(R5)3, alkenyl, or acyl, each optionally substituted with 0, 1 or multiple R6;
R3 is alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R6;
R4 is hydrogen, —C(O)R5, or —CH2OC(O)R5;
R5 is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R6;
R6 is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, heteroaryl, heterocyclyl, or thioalkyl, each optionally substituted with 0, 1, or multiple R7; and
R7 is hydrogen, alkyl, aryl, or halo.
Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.
It will be understood by the those skilled in the art that the following terms may include generic “R”-groups within their definitions, e.g., “the term alkoxy refers to an —OR substituent”. It is also understood that within the definitions for the following terms, these “R” groups are included for illustration purposes and should not be construed as limiting or being limited by substitutions about Formula I.
The term “alkyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. In some exemplary embodiments, the term “alkyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including containing from 1 to 12 carbon atoms, from 1 to 6 carbons, or from 1 to 4 carbons.
The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like. In some exemplary embodiments, the term “alkenyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including containing from 1 to 12 carbon atoms, from 1 to 6 carbons, or from 1 to 4 carbons.
The term “alkynyl” refers to a branched or unbranched carbon chain containing one or more triple bonds including, but not limited to, propynyl, butynyl and the like. In some exemplary embodiments, the term “alkynyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including containing from 1 to 12 carbon atoms, from 1 to 6 carbons, or from 1 to 4 carbons.
The term “aryl” refers to any aromatic, mono- or bi-cyclic, containing 0 heteroatoms.
The term “heterocycle” refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms. In some exemplary embodiments, the one or more heteroatoms are independently selected from nitrogen, oxygen, phosphorous, and sulfur.
The term “alkoxy” refers to an —OR substituent.
The term “cyano” refers to a —C≡N substituent.
The term “hydroxyl” refers to an —OH substituent.
The term “amino” refers to a —NR2 substituent.
The term “arylalkoxy” refers to —O(CH2)n—Ar where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.
The term “nitro” refers to a —NO2 substituent.
The term thioalkyl refers to an —SR substituent.
Throughout the disclosure, reference to the compounds of Formula I is read as also including diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, and hydroiodide.
It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.
Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.
Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
In one exemplary embodiment, a compound of Formula I is provided.
                wherein        X is hydrogen or C(O)R3;        Y is hydrogen, C(O)R3, or Q;        Q is        
                R1 is hydrogen, alkyl, alkenyl, aryl, alkoxy, or acyl, each optionally substituted with 0, 1 or multiple R6;        R2 is hydrogen, alkyl, aryl, —Si(R5)3, alkenyl, or acyl, each optionally substituted with 0, 1 or multiple R6;        R3 is alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R6;        R4 is hydrogen, —C(O)R5, or —CH2OC(O)R5;        R5 is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R6; R6 is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, heteroaryl, heterocyclyl, or thioalkyl, each optionally substituted with 0, 1, or multiple R7; and        R7 is hydrogen, alkyl, aryl, or halo.        
In one more particular embodiment, X and Y are hydrogen. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6, and R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, X is C(O)R3 and Y is hydrogen. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6, and R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, X is hydrogen and Y is Q. In another more particular embodiment of any of the above embodiments, R4 is hydrogen. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6, and R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R4 is —C(O)R5 or —CH2OC(O)R5. In another more particular embodiment of any of the above embodiments, R5 is chosen from alkyl and alkoxy, each optionally substituted with 0, 1, or multiple R6. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R1 is chosen from alkyl and aryl, each optionally substituted with 0, 1 or multiple R6, and R2 is chosen from hydrogen, alkyl, aryl, and acyl, each optionally substituted with 0, 1 or multiple R6. In another more particular embodiment of any of the above embodiments, R5 is chosen from —CH3, —CH2OCH2CH3, and —CH2CH2OCH3.